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WO2003011205A2 - Produits d'encapsulation assurant une liberation controlee ou prolongee - Google Patents

Produits d'encapsulation assurant une liberation controlee ou prolongee Download PDF

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Publication number
WO2003011205A2
WO2003011205A2 PCT/US2001/047180 US0147180W WO03011205A2 WO 2003011205 A2 WO2003011205 A2 WO 2003011205A2 US 0147180 W US0147180 W US 0147180W WO 03011205 A2 WO03011205 A2 WO 03011205A2
Authority
WO
WIPO (PCT)
Prior art keywords
encapsulated product
cellulose
product
drugs
therapeutic
Prior art date
Application number
PCT/US2001/047180
Other languages
English (en)
Other versions
WO2003011205A3 (fr
Inventor
S. Rao Cherukuri
Vittorino Ravelli
Original Assignee
Capricorn Pharma, Inc.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Capricorn Pharma, Inc. filed Critical Capricorn Pharma, Inc.
Priority to AU2002239555A priority Critical patent/AU2002239555A1/en
Priority to EP01987325A priority patent/EP1581160A4/fr
Publication of WO2003011205A2 publication Critical patent/WO2003011205A2/fr
Publication of WO2003011205A3 publication Critical patent/WO2003011205A3/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23G—COCOA; COCOA PRODUCTS, e.g. CHOCOLATE; SUBSTITUTES FOR COCOA OR COCOA PRODUCTS; CONFECTIONERY; CHEWING GUM; ICE-CREAM; PREPARATION THEREOF
    • A23G3/00—Sweetmeats; Confectionery; Marzipan; Coated or filled products
    • A23G3/34—Sweetmeats, confectionery or marzipan; Processes for the preparation thereof
    • A23G3/346—Finished or semi-finished products in the form of powders, paste or liquids
    • A—HUMAN NECESSITIES
    • A21—BAKING; EDIBLE DOUGHS
    • A21D—TREATMENT OF FLOUR OR DOUGH FOR BAKING, e.g. BY ADDITION OF MATERIALS; BAKING; BAKERY PRODUCTS
    • A21D13/00—Finished or partly finished bakery products
    • A21D13/80—Pastry not otherwise provided for elsewhere, e.g. cakes, biscuits or cookies
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23G—COCOA; COCOA PRODUCTS, e.g. CHOCOLATE; SUBSTITUTES FOR COCOA OR COCOA PRODUCTS; CONFECTIONERY; CHEWING GUM; ICE-CREAM; PREPARATION THEREOF
    • A23G3/00—Sweetmeats; Confectionery; Marzipan; Coated or filled products
    • A23G3/34—Sweetmeats, confectionery or marzipan; Processes for the preparation thereof
    • A23G3/343—Products for covering, coating, finishing, decorating
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23G—COCOA; COCOA PRODUCTS, e.g. CHOCOLATE; SUBSTITUTES FOR COCOA OR COCOA PRODUCTS; CONFECTIONERY; CHEWING GUM; ICE-CREAM; PREPARATION THEREOF
    • A23G3/00—Sweetmeats; Confectionery; Marzipan; Coated or filled products
    • A23G3/34—Sweetmeats, confectionery or marzipan; Processes for the preparation thereof
    • A23G3/36—Sweetmeats, confectionery or marzipan; Processes for the preparation thereof characterised by the composition containing organic or inorganic compounds
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23G—COCOA; COCOA PRODUCTS, e.g. CHOCOLATE; SUBSTITUTES FOR COCOA OR COCOA PRODUCTS; CONFECTIONERY; CHEWING GUM; ICE-CREAM; PREPARATION THEREOF
    • A23G3/00—Sweetmeats; Confectionery; Marzipan; Coated or filled products
    • A23G3/34—Sweetmeats, confectionery or marzipan; Processes for the preparation thereof
    • A23G3/36—Sweetmeats, confectionery or marzipan; Processes for the preparation thereof characterised by the composition containing organic or inorganic compounds
    • A23G3/362—Sweetmeats, confectionery or marzipan; Processes for the preparation thereof characterised by the composition containing organic or inorganic compounds containing inorganic compounds
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23G—COCOA; COCOA PRODUCTS, e.g. CHOCOLATE; SUBSTITUTES FOR COCOA OR COCOA PRODUCTS; CONFECTIONERY; CHEWING GUM; ICE-CREAM; PREPARATION THEREOF
    • A23G3/00—Sweetmeats; Confectionery; Marzipan; Coated or filled products
    • A23G3/34—Sweetmeats, confectionery or marzipan; Processes for the preparation thereof
    • A23G3/36—Sweetmeats, confectionery or marzipan; Processes for the preparation thereof characterised by the composition containing organic or inorganic compounds
    • A23G3/364—Sweetmeats, confectionery or marzipan; Processes for the preparation thereof characterised by the composition containing organic or inorganic compounds containing microorganisms or enzymes; containing paramedical or dietetical agents, e.g. vitamins
    • A23G3/368—Sweetmeats, confectionery or marzipan; Processes for the preparation thereof characterised by the composition containing organic or inorganic compounds containing microorganisms or enzymes; containing paramedical or dietetical agents, e.g. vitamins containing vitamins, antibiotics
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23G—COCOA; COCOA PRODUCTS, e.g. CHOCOLATE; SUBSTITUTES FOR COCOA OR COCOA PRODUCTS; CONFECTIONERY; CHEWING GUM; ICE-CREAM; PREPARATION THEREOF
    • A23G3/00—Sweetmeats; Confectionery; Marzipan; Coated or filled products
    • A23G3/34—Sweetmeats, confectionery or marzipan; Processes for the preparation thereof
    • A23G3/50—Sweetmeats, confectionery or marzipan; Processes for the preparation thereof characterised by shape, structure or physical form, e.g. products with supported structure
    • A23G3/54—Composite products, e.g. layered, coated, filled
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23G—COCOA; COCOA PRODUCTS, e.g. CHOCOLATE; SUBSTITUTES FOR COCOA OR COCOA PRODUCTS; CONFECTIONERY; CHEWING GUM; ICE-CREAM; PREPARATION THEREOF
    • A23G4/00—Chewing gum
    • A23G4/06—Chewing gum characterised by the composition containing organic or inorganic compounds
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23G—COCOA; COCOA PRODUCTS, e.g. CHOCOLATE; SUBSTITUTES FOR COCOA OR COCOA PRODUCTS; CONFECTIONERY; CHEWING GUM; ICE-CREAM; PREPARATION THEREOF
    • A23G4/00—Chewing gum
    • A23G4/06—Chewing gum characterised by the composition containing organic or inorganic compounds
    • A23G4/064—Chewing gum characterised by the composition containing organic or inorganic compounds containing inorganic compounds
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23G—COCOA; COCOA PRODUCTS, e.g. CHOCOLATE; SUBSTITUTES FOR COCOA OR COCOA PRODUCTS; CONFECTIONERY; CHEWING GUM; ICE-CREAM; PREPARATION THEREOF
    • A23G4/00—Chewing gum
    • A23G4/06—Chewing gum characterised by the composition containing organic or inorganic compounds
    • A23G4/12—Chewing gum characterised by the composition containing organic or inorganic compounds containing microorganisms or enzymes; containing paramedical or dietetical agents, e.g. vitamins
    • A23G4/126—Chewing gum characterised by the composition containing organic or inorganic compounds containing microorganisms or enzymes; containing paramedical or dietetical agents, e.g. vitamins containing vitamins, antibiotics
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23G—COCOA; COCOA PRODUCTS, e.g. CHOCOLATE; SUBSTITUTES FOR COCOA OR COCOA PRODUCTS; CONFECTIONERY; CHEWING GUM; ICE-CREAM; PREPARATION THEREOF
    • A23G4/00—Chewing gum
    • A23G4/18—Chewing gum characterised by shape, structure or physical form, e.g. aerated products
    • A23G4/20—Composite products, e.g. centre-filled, multi-layer, laminated
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L2/00—Non-alcoholic beverages; Dry compositions or concentrates therefor; Preparation or treatment thereof
    • A23L2/385—Concentrates of non-alcoholic beverages
    • A23L2/39—Dry compositions
    • A23L2/395—Dry compositions in a particular shape or form
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L27/00—Spices; Flavouring agents or condiments; Artificial sweetening agents; Table salts; Dietetic salt substitutes; Preparation or treatment thereof
    • A23L27/70—Fixation, conservation, or encapsulation of flavouring agents
    • A23L27/72—Encapsulation
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2013—Organic compounds, e.g. phospholipids, fats
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2013—Organic compounds, e.g. phospholipids, fats
    • A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
    • A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4808—Preparations in capsules, e.g. of gelatin, of chocolate characterised by the form of the capsule or the structure of the filling; Capsules containing small tablets; Capsules with outer layer for immediate drug release
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23G—COCOA; COCOA PRODUCTS, e.g. CHOCOLATE; SUBSTITUTES FOR COCOA OR COCOA PRODUCTS; CONFECTIONERY; CHEWING GUM; ICE-CREAM; PREPARATION THEREOF
    • A23G2200/00—COCOA; COCOA PRODUCTS, e.g. CHOCOLATE; SUBSTITUTES FOR COCOA OR COCOA PRODUCTS; CONFECTIONERY; CHEWING GUM; ICE-CREAM; PREPARATION THEREOF containing organic compounds, e.g. synthetic flavouring agents
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23G—COCOA; COCOA PRODUCTS, e.g. CHOCOLATE; SUBSTITUTES FOR COCOA OR COCOA PRODUCTS; CONFECTIONERY; CHEWING GUM; ICE-CREAM; PREPARATION THEREOF
    • A23G2200/00—COCOA; COCOA PRODUCTS, e.g. CHOCOLATE; SUBSTITUTES FOR COCOA OR COCOA PRODUCTS; CONFECTIONERY; CHEWING GUM; ICE-CREAM; PREPARATION THEREOF containing organic compounds, e.g. synthetic flavouring agents
    • A23G2200/04—COCOA; COCOA PRODUCTS, e.g. CHOCOLATE; SUBSTITUTES FOR COCOA OR COCOA PRODUCTS; CONFECTIONERY; CHEWING GUM; ICE-CREAM; PREPARATION THEREOF containing organic compounds, e.g. synthetic flavouring agents containing vitamins, antibiotics, other medicaments
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23G—COCOA; COCOA PRODUCTS, e.g. CHOCOLATE; SUBSTITUTES FOR COCOA OR COCOA PRODUCTS; CONFECTIONERY; CHEWING GUM; ICE-CREAM; PREPARATION THEREOF
    • A23G2220/00—Products with special structure
    • A23G2220/20—Products with special structure with a composite structure, e.g. laminated products, coated products, microstructures, e.g. with encapsulated ingredients

Definitions

  • the present invention relates to an encapsulation process, and in particular, an alternate encapsulation process for concentrating additives using compression. Also, the present inventive subject matter relates to encapsulation products that provide controlled or extended release of actives.
  • chewable articles include food items such as food items, confectionery items and chewing gum.
  • the chewable articles often include various types of active agents or ingredients within the chewable articles. Examples of such active ingredients include flavors, sweeteners, colors, medicaments, pharmaceuticals, vitamins, minerals, and other effervescent agents .
  • protection systems including providing a protective coating around the active ingredient or encapsulating the active ingredient.
  • Such protective systems have been employed for various reasons, such as for protection of the active ingredient, both while on the shelf and during use, and for prolonged release in the oral cavity.
  • liquid suspending media water-in-oil emulsions and oil-in-water emulsions
  • interfacial and in situ polymerization solvent evaporation from emulsions
  • desolvation complex coacervation
  • polymer and polymer incompatibality gelation, and pressure extrusion.
  • pressure extrusion One of skill in the art will be familiar with each of these classifications.
  • Schobel U.S. Patent No. 4,568,560, discloses encapsulated fragrances and flavors for use in denture cleanser compositions. Schobel discloses encapsulating a solid particulate flavoring agent or fragrance with a film of an acrylic polymer and ethylcellulose. The encapsulation is accomplished utilizing a fluidized bed of the flavoring agent or fragrance.
  • U.S. Patent No. 4,981,698 discloses a delivery system for sweeteners that comprises a first high intensity sweetener encapsulated in a first core coating, and a second outer hydrophilic coating containing up to the solubility limit of the second coating of a second sweetener.
  • the delivery system offers enhanced up front sweetness intensity in combination with prolonged sweetness duration, and improved protection and stability of the sweetener.
  • Cherukuri et al. U.S. Patent No. 5,004,595, discloses a free-flowing particulate delivery system for providing enhanced flavor and sweetness to comestible products.
  • the delivery system includes an encapsulating matrix that protects flavor in a core.
  • the microencapsule comprises a flavoring agent and a resin in the core, and a coating layer over the core.
  • the core is encapsulated by emulsion of a flavoring agent and a resin with a coating layer prepared by complex coacervation of a mixture of two or more colloidal materials.
  • Kehoe U.S. Patent No. 4,975,270, discloses elastomer encased active ingredients.
  • the active ingredients are physically encased in non-porous, chewable particles of elastomer. The particles are then incorporated into articles of commerce.
  • Ueda et al. U.S. Patent No. 4,874,549, disclose a time-controlled system in which a drug is diffused into a patient after the explosion of a membrane at a given period of time after ingestion.
  • the system is comprised of a preparation in the form of a bead or granule which makes up a core, a drug, a swelling agent and an outer membrane made up of a water- insoluble coating material.
  • U.S. Patent No. 5,508,040 discloses a multiparticulate pulsatile drug delivery system.
  • the system is comprised of a large number of pellets containing a drug and a water soluble osmotic agent.
  • the pellets are an agglomerate of sugar seeds with the drugs spray-coated thereon.
  • the disadvantages include the need for heat and moisture in order to properly form the encapsulated final product. Also, most encapsulation methods are complex and consume large amounts of time in order to obtain the final encapsulated product. Further, current encapsulated ingredients vary in size from nanometers to about 400 microns, and the active ingredients are not uniformly distributed throughout the encapsulated product.
  • Applicant has unexpectedly produced an extended or controlled release encapsulated product, comprising: a) at least one active ingredient; b) at least one erodible polymer; and c) at least one lubricating material; and d) wherein said product is in the form of a caplet having a diameter from about 1 millimeter to about 7 millimeters and a length from about 1 millimeter to about 7 millimeters.
  • the erodible polymer is a water soluble polymer.
  • the erodible polymer is a water insoluble polymer.
  • a further preferred embodiment is drawn to a pulsating release encapsulated product, comprising: a) at least one active ingredient; b) at least two erodible polymers, each of said erodible polymers having a different rate of dissolution; and c) at least one lubricating material; and d) wherein said product is in the form of a caplet having a diameter from about 1 millimeter to about 7 millimeters and a length from about 1 millimeter to about 7 millimeters.
  • a still further preferred embodiment is drawn to a pulsating release product, comprising a capsule having a plurality of caplets, said caplets comprising: a) at least one active ingredient; b) at least one erodible polymer; c) at least one lubricating material; and d) wherein said caplet has a diameter from about 1 millimeter to about 7 millimeters and a length from about 1 millimeter to about 7 millimeters; and wherein at least one of said plurality of caplets is prepared from an erodible polymer having a first dissolution rate, and at least another of said plurality of caplets is prepared from another erodible polymer having a second dissolution rate, and said first dissolution rate is not equal to said second dissolution rate.
  • An advantage of method of the inventive subject matter is that no heat nor moisture is required for forming the encapsulated product. High levels of active ingredients are obtainable in the products of the inventive subject matter, even though heat or moisture is not required for forming the encapsulated product.
  • the encapsulated product of the present inventive subject matter has a uniform active ingredient content and may be strong enough to withstand mechanical pressure both in the processing of the product, and in the chewing of the product in the mouth so that the active ingredients are released in the stomach.
  • the encapsulated product of the present invention is a caplet containing a surprisingly high amount of an active ingredient and providing excellent controlled or extended release properties. Applicants have unexpectedly determined that active ingredients can be compressed with high load into a small encapsulated product.
  • the controlled release products of the present inventive subject matter are designed to produce a sustained concentration of pharmaceutical in the blood.
  • the advantages of the controlled or extended release products of the present inventive subject matter include reduced toxicity and sustained efficacy of the active ingredients; decreased frequency of dosing, resulting in improved patient compliance, reduced patient care; and possibly reduced amount of drug used.
  • the controlled or extended release encapsulated product of the present inventive subject matter is a caplet shaped like a capsule and having a diameter from about 1 millimeter to about 7 millimeters and a length from about 1 millimeter to about 7 millimeters.
  • the diameter of the encapsulated product is about 3 millimeters and the length is about 3 millimeters.
  • the caplets may be coated with a thin surface film to protect the product from moisture or water absorption, from flavor release in the final product system, and from heat and rupture during processing and chewing.
  • mammal includes without limitation any mammalian subject, such as mice, rats, guinea pigs, cats, dogs, human beings, cows, horses, sheep or other livestock.
  • active ingredient includes without limitation: flavors, sweeteners, herbal ingredients, pharmaceuticals, vitamins, minerals, and mixtures thereof.
  • controlled release or extended release relates to the release rates of the pharmaceutical from the encapsulated product into the mammal.
  • the terms refer to the release of the drug over a period of time, for example from one hour to twenty-four hours.
  • - Erodible matrixes either multi-particulate or monolithic, that release the included active substance, generally poorly water soluble, by controlled erosion of the system.
  • - Osmotic systems in monolithic, tablets form that release the drug, soluble in digestive fluids, through a calibrated hole in the osmotic membrane surrounding the tablet .
  • the active ingredient to be released into a mammal is incorporated into an erodible polymer matrix.
  • a general method for preparing a controlled- release encapsulated product encompasses the following steps. First, the active ingredient is mixed with a suitable erodible polymer. The active ingredient may be present in amounts from 0.001 to 70.0% by weight of the final encapsulated product. The erodible polymer may be present from 10.0 to 70.0% by weight of the final encapsulated product.
  • the erodible polymer may be either water soluble or water insoluble.
  • Water soluble polymers useful in the present inventive subject matter include, without limitation, sodium carboxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, propylene glycol alginate, sodium alginate, carboxymethyl cellulose and mixtures thereof.
  • water insoluble polymers that are useful in the present inventive subject matter include, without limitation, cellulose acetate, ethyl cellulose, cellulose acetate methyl carbamate, methylcarbamate, polydiethylaminomethylstyrene, ethyl cellulose, cellulose acetate, cellulose diacetate, cellulose triacetate, cellulose alkanylate, monoalkenytes, dialkenytes, trialkenytes, mono-, di- and tri-arolyates, cellulose trivalerate, cellulose trioctanoate, cellulose tripionate, celluslose diesters, cellulose disuccinate, cellulose acetate valerate, cellulose acetaldehyde, dimethylcellulose acetate, cellulose dimethylaminoacetate, semipermeable sulfonated polystyrenes, semipermeable styrenes, and mixtures thereof.
  • the active ingredient/polymer mixture is then granulated using a suitable binder.
  • the binder is generally present in amounts of 1.0 to 10.0% by weight of the final encapsulated product.
  • Binders suitable for use in the present inventive subject matter include, without limitation, plasdone K-29/32, povidone K30, carboxymethylcellulose sodium, ethylcellulose, methylcellulose, alginic acid and mixtures thereof.
  • the mixture is passed through a mesh, preferably a mesh no. 10, and allowed to air dry. After air-drying, the mixture is passed through another mesh, preferably a no . 20 mesh.
  • the granulated mixture is lubricated with a lubricant and compressed into capsules with the sizes listed above.
  • the lubricant or lubricating material forms a film around the granules and helps the material flow, compress and eject from the tableting machine.
  • the lubricant or lubricating material may be present in levels up to 5% by weight of the final composition. Examples of usable lubricating materials include, without limitation, fats, emulsifiers, waxes, magnesium stearate, calcium stearate, talc, starches, silicon dioxide, and mixtures thereof.
  • fats, or fatty materials useful herein include, without limitation, water-insoluble, inert hydrocarbon fats or oils, or their derivatives and mixtures thereof.
  • Such fats or fatty materials include, for example and without limitation, cocoa butter, hydrogenated vegetable tallow, hydrogenated vegetable oils, and derivative mixtures thereof.
  • emulsifiers useful herein include, without limitation, alkyl aryl sulfonates, alkyl sulfates, sulfonated amides and amines, sulfated and sulfonated esters and ethers, alkyl sulfonates, polyethoxylated esters, mono- and diglycerides, diactyl tartaric esters of monoglyderides, polyglycerol esters, sorbitan esters and ethoxylates, lactylated esters, propylene glycol esters, sucrose esters and mixtures thereof.
  • waxes useful herein include, without limitation, amorphous waxes, anionic emulsifying waxes, bleached waxes, caranda waxes, cetyl esters, cationic emulsifying waxes, microcrystalline waxes, paraffins, refined waxes and mixtures thereof.
  • the use of particular fats, emulsifiers or waxes may allow the encapsulated product of the present inventive subject matter to aid in providing controlled or sustained release of the active ingredient.
  • the controlled release occurs due to the entrapment of the active material in the particular fat, emulsifier or wax.
  • the coating provides protection of the active ingredients from moisture or water absorption.
  • the coating may also allow the release of the active ingredient in the stomach of the individual, and not in the mouth thereof.
  • the encapsulated product is coated with a polymeric coating to form an extended release formulation.
  • the extended release formulations are where the mechanism of release is driven, predominantly, by the osmotic pressure.
  • the encapsulated products are formulated with osmotic ingredients and coated with semipermeable film forming polymers to achieve zero-order release.
  • the advantages of this formulation include the combination of the mechanism of the control of the release based on the osmotic pressure (finely tuned and independent from the motility, pH, composition of the digestive fluids and food) with the concept of multiple units (improved inter and intra- subjects variability of absorption) .
  • Active ingredients can be any pharmacologically active substance to be administered by the oral route and included in a solid dosage form.
  • Osmotic ingredients can be any active principle ingredient with a solubility in aqueous media, in the range of pH from 1 to 7 and in an amount of not less than 0.1%.
  • any inorganic salt may be used which is highly dissociated in aqueous media in the range of pH from 1 to 7 and suitable to be included in pharmaceutical preparations for oral administration.
  • Semi-permeable film forming polymers can be high molecular weight derivatives of cellulose which are insoluble in water as ethylcellulose with a degree of ethylation between 43% and 50%, cellulose acetate with 30%-45% of acetyl value, polyvinylacetate, ammonium methacrylate co-polymers.
  • Suitable plasticizers can be added in the range of 5% to 35%.
  • the film thickness may vary from 20 ⁇ m to lOO ⁇ m to achieve the desired extended release profile.
  • the size of encapsulated products may vary between 2mm to 3mm of diameter and height. Depending on the composition of the core and on the type and thickness of the film different zero order kinetics can be achieved.
  • This encapsulated product formulation can be applied to any controlled release applications including OTC & Rx Pharmaceuticals, and Nutritional applications.
  • the encapsulated product is coated with a polymeric coating to form a delayed release formulation.
  • the delayed release, monolithic, oral dosage form is based on osmotic pressure and then a crown coating in the coating polymer formed in si tu when the dose is ingested.
  • Oral dosage forms have heretofore been generally based on osmotic pressure by preparing a core, usually in the form of a tablet, containing the active substance dispersed in a combination of ingredients able to generate an osmotic pressure, when contained by an osmotic membrane.
  • a core usually in the form of a tablet
  • the release from such systems is obtained with a calibrated hole in the membrane which regulates, together with the level of osmotic pressure generated by the intrinsic characteristics of the tablet core, the rate of release.
  • tablets with swelling polymers, osmotic ingredients and active substance, with a cone protuberance on one side are then coated with semi-permeable film-forming polymer.
  • the thickness of the film is lower on the cone.
  • the film brakes on the cone because the lower thickness and the content of the vesicle (the coated tablet) is released.
  • the time to break is regulated by the thickness of the film and the height of the cone.
  • Active ingredients can be any pharmacologically active substance to be administered by the oral route and included in a solid dosage form.
  • Osmotic ingredients can be any active principle ingredient with a solubility in aqueous media, in the range of pH from 1 to 7 and in amounts not less than 0.1%.
  • Any inorganic salt may be used which is highly dissociated in aqueous media in the range of pH from 1 to 7 and suitable to be included in pharmaceutical preparations for oral administration.
  • Swelling polymers can be polycarbophyls and hydroxypropylmethylcellulose of different viscosity such as from 4,000 to 100,000 cps.
  • the diameter of the tablets can vary from 5 mm to 10 mm.
  • the thickness can vary from 3 mm to 5 mm.
  • the height of the cone can vary from 0.5 mm to 1.0 mm.
  • the shape of the protuberance is conical with the diameter of the base that can vary from 0.8 to 1.3 mm.
  • Semi-permeable film forming polymers can be high molecular weight derivatives of cellulose which are insoluble in water as ethylcellulose with a degree to ethylation between
  • Suitable plasticizers can be added in the range of 5% to 35%.
  • the film thickness may vary from 20 ⁇ m to 150 m. This formulation can be applied to any modified release applications including OTC & Rx Pharmaceuticals, and Nutritional applications.
  • the controlled release of the encapsulated product provide "pulses” or “pulsating release” of the active ingredients.
  • pulses or “pulsating release”
  • Applicants mean that the active ingredient is released at different time intervals while in the body of the mammal.
  • pulsesating Applicants also mean that the release of the active ingredients may be continuous, discontinuous, extended or sustained.
  • the "pulsating" aspect of the release of the active ingredients means the discontinuous release of the actives.
  • the present inventive subject matter provides pulsating delivery of the active ingredient by taking advantage of the different characteristics of the different the polymer erodible polymers used in the encapsulated products.
  • the encapsulated product is prepared with at least two erodible polymers, each having a different rate of dissolution in the body of the mammal in which the encapsulated product is introduced.
  • the encapsulated product may be made with two or more erodible polymers, at least one that erodes quickly in the body to provide immediate dissolution of the drug and at least another that does not erode as quickly, thus delaying release of the active ingredient until a desired time.
  • an important aspect of this embodiment of the present inventive subject matter is the incorporation of at least two erodible polymers having different rates of dissolution.
  • the present inventive subject matter contemplates the use of both water soluble polymers and water insoluble polymers for this preferred embodiment. Examples of water soluble and water insoluble polymers are listed above.
  • the erodible polymers used to achieve the pulsating release of the active ingredient may be water soluble, water insoluble, or a mixture thereof.
  • One of ordinary skill in the art will be able to easily determine which polymers are suitable to achieve the desired pulsating release of the active ingredients based on the dissolution rates of the various erodible polymers.
  • the pulsating effect is achieved by incorporating into a standard capsule encapsulated products prepared from different erodible polymers.
  • the active ingredient is incorporated into multiple encapsulated products using two or more different erodible polymers, with each encapsulated product being prepared with a different erodible polymer.
  • the different encapsulated products are included in a standard capsule which is taken by the mammal.
  • the encapsulated products will erode at different rates based upon the erodible polymers with which the products were made, providing a pulsating release profile of the active ingredients.
  • one of ordinary skill in the art will be able to easily determine which polymers are suitable to achieve the desired pulsating release of the active ingredients based on the dissolution rates of the various erodible polymers.
  • the present inventive subject matter also contemplates site-specific delivery of the active ingredients by different modes of introduction of the active ingredient into the body.
  • the different modes include, for example, introduction of the encapsulated products rectally, which will allow introduction of the products directly into the large bowel of the mammal. In this way, the encapsulated products will act much like a suppository, providing controlled release of the active ingredients while at the same time by-passing the oral route of delivery.
  • Another example of a non-oral controlled delivery of active ingredients by the present inventive subject matter is to have the inventive encapsulated products implanted into the body.
  • the encapsulated products produced and preserved sterile until use, would be implanted directly into the region of the body where the need for the active ingredient is the greatest. Then, as the bodily fluids erode the erodible polymers of the encapsulated products, the active ingredients would be released directly to the site which needs the active ingredients the most.
  • site specific delivery of active ingredients according to the present inventive subject matter is to apply the inventive encapsulated products directly to a cut or abrasion on the skin of the mammal being treated. The size of the inventive encapsulated products allows for direct application to the wound in order to directly deliver the needed active ingredient.
  • the inventive encapsulated products will be held in place with a bandage, thus keeping optimal contact between the encapsulated products and the wound.
  • the controlled release encapsulated products may have the same characteristics as described above for oral delivery of active ingredients. That is, the controlled release may be zero order, or may provide a pulsating effect, as is defined above. Further, the pulsating effect may be the result of two or more different erodible polymers being incorporated into the same inventive encapsulated product, or the pulsating effect may be due to the presence of multiple encapsulated products having been made from different erodible polymers having different rates of dissolution.
  • the amount of active material present in the inventive compositions will vary depending on the particular active used, but generally will be present in an amount of about 0.001% to 70% by weight of the composition.
  • the active ingredients used in the inventive compositions are prophylactic or therapeutic active ingredients.
  • Prophylactic or therapeutic active materials which can be used in the present invention are varied.
  • a non-limiting list of such materials includes the following: antibiotics, antitussives, antihistamines, decongestants, alkaloids, mineral supplements, laxatives, antacids, ion exchange resins, anti-cholesterolemics, antiarrhythmics, antipyretics, analgesics, appetite suppressants, expectorants, anti-anxiety agents, anti-ulcer agents, anti-inflammatory substances, coronary dilators, cerebral dilators, peripheral vasodilators, anti-infectives, psycho-tropics, antimanics, stimulants, gastrointestinal agents, sedatives, antidiarrheal preparations, anti-anginal drugs, vasodialators, anti-hypertensive drugs, vasoconstrictors, migraine treatments, antibiotics, tranquilizers, anti-psychotics, antitumor drugs, anticoagulants, antithrombotic drugs, hypontics, anti-emetics, anti-nausants, anti-convulsants, neuromus
  • Preferred therapeutic active materials contemplated for use in the present inventive subject matter are analgesics.
  • analgesics useful in the present inventive subject matter, and which are the preferred therapeutic active ingredients include, without limitation, aspirin, acetaminophen, ibuprophen and mixtures thereof.
  • Another preferred active material can be selected from the class of prophylactic, abortive or analgesic drugs used to treat migraines.
  • Migraines are defined as headaches that last 4 to 72 hours wherein the patient experiences moderate to severe cranial throbbing. Migraines are also associated with nausea, vomiting, or sensitivity to light, sound or smell.
  • ⁇ -blockers For prophylactic treatment of migraines, ⁇ -blockers, calcium channel blockers, tricyclic antidepressants, or anticonvulsants can be used.
  • drugs indicated for prophylactic treatment include amitriptyline, methysergide, popranolol, valproate, and verapamil.
  • serotonin receptor activators such as eletriptan, ergotamine, naratriptan, rizatriptan benzoate, sumatriptan succinate, and zolmitriptan can be used.
  • Ergot alkaloid derivatives such as ergoamine tartrate and dihydroergotamine are also effective.
  • Dopamine antagonist anti-emetics such as dimenhydrinate, metoclopramide and prochlorperazine, while indicated for the treatment of nausea, can also be used even if nausea is not prominent.
  • acetaminophen, aspirin, non- asteroidal anti-inflammatory drugs ("NSAID”) and opioids can be used in the present invention.
  • any class of drug indicated for migraine treatment may be used in the present invention.
  • sumatriptan succinate may be incorporated into the encapsulated products of the present invention to effectively deliver sumatriptan succinate to a patient in need thereof.
  • sumatriptan succinate can be formulated with the present invention in doses ranging from 25, 50, to 100 mg daily. All the examples are non-limiting and it will be understood that other migraine therapeutics may be used with the present inventive subject matter.
  • Yet another preferred active material used in the composition of the present inventive matter is a psychotropic. Psychotropics are used to treat depression, schizophrenia, anxiety disorders, attention deficit order, obsessive compulsive disorder, senile dementia and certain sleep disorders.
  • the classes of drugs used in treating depression include selective serotonin reuptake inhibitors ("SSRI's”), heterocyclic antidepressants, monoamine oxidase inhibitors ("MAOI's”), serotonergic-noradrenergics, 5-HT 2 antagonists and catecholaminergics .
  • SSRI' S include fluoxetine HC1, sertraline HC1, paroxetine HC1, and fluvoxamine.
  • heterocyclic antidepressants include amitriptyline, nortriptyline, imipramine, desipramine, doxepin, trimipramine, clomipramine, protriptyline, amoxapine, and maprotiline.
  • Examples of MAOI's include phenelzine and tranylcypromine.
  • An example of a serotonergic-noradrenergics includes venlafaxine HC1.
  • Examples of 5-HT 2 antagonists include trazadone, nefazodone, and mirtazapine.
  • An example of a catecholaminergics includes bupropion. All examples are non- limiting and it will be understood that psychotropics of the disclosed classes may be used with the present inventive subject matter.
  • any class of psychotropic drug indicated for treating depression may be used in the present invention.
  • fluoxetine HC1 may be incorporated into the encapsulated products of the present invention to effectively deliver fluoxetine HC1 to a patient in need thereof.
  • fluoxetine HC1 can be formulated with the present invention in doses ranging from about 10 to 60 mg daily.
  • doses ranging from about 10 to 60 mg daily.
  • One of ordinary skill in the art will be able to determine the proper dosage for the remaining disclosed drugs.
  • benzodiazepines may be used with the present inventive subject matter.
  • Specific examples include alprazolam, chlordiazepoxide, clonazepam, clorazepate, diazepam, lorazepam, and oxazepam.
  • any class of psychotropic drug indicated for anxiety treatment may be used in the present invention.
  • alprazolam may be incorporated into the encapsulated products of the present invention to effectively deliver alprazolam to a patient in need thereof.
  • alprazolam can be formulated with the present invention in doses ranging from about 0.25 to 0.50 mg to be taken three times daily.
  • One of ordinary skill in the art will be able to determine the proper dosage for the remaining disclosed drugs.
  • drugs belonging to the categories of benzodiazepines, imidazopyridines, antidepressants and non-prescription hypnotics may be used with the present inventive subject matter.
  • benzodiazepines useful for the treatment of insomnia include midazolam, triazolam, oxazepam, temazepam, lorazepam, estazolam, nitrazepam, diazepam, quazepam, flurazepam, zopiclone and clorazepate.
  • An example of an imidazopyridine includes zolpidem and zolpidem tartarate.
  • antidepressants include amityiptyline and doxepin.
  • zolpidem may be incorporated into the encapsulated products of the present invention to effectively deliver zolpidem to a patient in need thereof.
  • zolpidem can be formulated with the present invention in doses ranging from about 5.0 to 30.0 mg daily, the preferred range being from about 5.0 to 10.0 mg daily.
  • doses ranging from about 5.0 to 30.0 mg daily, the preferred range being from about 5.0 to 10.0 mg daily.
  • One of ordinary skill in the art will be able to determine the proper dosage for the remaining disclosed drugs.
  • all the examples are non-limiting and it will be understood that other psychotrpoics may be used with the present inventive subject matter.
  • Still yet another preferred active material used in the composition of the present inventive matter is a gastrointestinal therapeutic.
  • Gastrointestinal therapeutics are used to treat gastritis, nausea and vomiting, gastroesophegal reflux disease, colitis, Crohn's disease and diarrhea.
  • Classes of drugs include proton pump inhibitors, histamine H 2 receptor antagonists, terpene analogs, and NSAID'S.
  • drugs such as omeprazole, lansoprazole, ranitidine HCl, famotidine, nizatidine, teprenone, cimetidine, rabeprazole sodium, and sulpiride can be used in the compositions of the present inventive subject matter.
  • drugs such as ondansetron HCl, granisetron HCl, dolasetron mesylate, and tropisetron may be used.
  • omeprazole may be incorporated into the encapsulated products of the present invention to effectively deliver omeprazole to a patient in need thereof.
  • omeprazole can be formulated with the present invention in doses ranging from about 10.0 to 60.0 mg daily, the preferred range being from about 15.0 to 25.0 mg daily.
  • doses ranging from about 10.0 to 60.0 mg daily, the preferred range being from about 15.0 to 25.0 mg daily.
  • One of ordinary skill in the art will be able to determine the proper dosage for the remaining disclosed drugs.
  • all the examples are non-limiting and it will be understood that other gastrointestinal therapeutics may be used with the present inventive subject matter.
  • Cardiovascular therapeutics treat hypertension, angina, myocardial infarction, congestive heart failure, acute coronary syndrome, edema, ventricular tachycardia, hyperaldosteronism, ventricular arrhythmia, cardiac insufficiency, atrial fibrillation, arterial occlusion, cardiac decompensation, and microcirculation activation.
  • a related class of cardiovascular therapeutics are cholesterol reducers such as 3-hydroxy-3-methylglutaryl coenzymeA ("HMG-CoA”) reductase inhibitors.
  • HMG-CoA inhibitors work by blocking an enzyme used to make cholesterol. Blocking cholesterol thereby treats hypercholesterolemia which is a significant cause of cardiovascular disease.
  • drugs such as simvastin, atorvastatin calcium, pravastatin sodium, pravastatin, lovastatin, fluvastatin sodium, cerivastatin sodium can be used in the compositions of the present inventive subject matter.
  • drugs such as nifedipine, amlodipine besylate, losartan potassium, lisinopril, felodipine, benazepril HCl, ramipril, irbesartan, verapamil HCl, bisoprolol fumarate and hydrochlorothiazide, amlodipine and benazepril HCl, clonidine, candesartan, cilexetil, diltiazem, nicardipine, imidapril, trandolapril, eprosartan mesylate, nilvadipine, verapamil HCl, temocapril, prazosin HCl, isradipine, cilazapril, celiprolol, bisoprolol, betazolol HCl, ramipril, nisoldipine, lisinopril,
  • drugs such as dioxin, carvedilol, spironolactone, trandolapril, and bisoprolol can be used in the compositions of the present inventive subject matter.
  • simvastin may be incorporated into the encapsulated products of the present invention to effectively deliver simvastin to a patient in need thereof.
  • simvastin can be formulated with the present invention in doses ranging from about 5.0 to 80 mg daily.
  • One of ordinary skill in the art will, be able to determine the proper dosage for the remaining disclosed drugs.
  • all the examples are non-limiting and it will be understood that drugs from the disclosed classes may also be used with the present inventive subject matter.
  • Still another preferred active material used in the composition of the present invention is a therapeutic useful for treating allergic rhinitis.
  • the classes of compounds useful for treating allergic rhinitis include alkylamines, ethanolamines, ethylenediamines, piperazines, phenothiazine, piperdines, and nonsedating compounds.
  • Other drugs which can also be used are fluticasone propionate, mometasone furoate, epinastine, beclomethasone dipropionate, triamcinolone acetonide, budesonide, and azelastine.
  • loratadine may be incorporated into the encapsulated products of the present invention to effectively deliver loratadine to a patient in need thereof.
  • loratadine can be formulated with the present invention in doses ranging from about 5.0 to 15 mg daily, with 15mg daily being the preferred dosage.
  • doses ranging from about 5.0 to 15 mg daily, with 15mg daily being the preferred dosage.
  • One of ordinary skill in the art will be able to determine the proper dosage for the remaining disclosed drugs.
  • all the examples are non-limiting and it will be understood that other allergic rhinitis therapeutics may be used with the present inventive subject matter.
  • Still yet another preferred active material used in the composition of the present invention is a therapeutic useful for treating osteoarthritis or rheumatoid arthritis.
  • Rheumatoid arthritis is defined as non-specific, symmetrical inflammation of the peripheral joints, potentially resulting in progressive destruction of articular and periarticular structures. Osteoarthritis is characterized by loss of articular cartilage and hypertrophy of bone. Although osteoarthritis is a degenerative bone disease, symptoms associated with rheumatoid arthritis such as inflammation of the joints occur in a patient diagnosed with osteoarthritis. Accordingly, therapeutics treating rheumatoid arthritis can also be administered to an osteoarthritic patient.
  • Classes of drugs indicated for osteoarthritis and rheumatoid arthritis include cycloxygenase-2 inhibitors, NSAID'S, biologic response modifiers, pyrimidine synthesis inhibitors and hyaluronic acid.
  • Specific examples of osteoarthritis and rheumatoid arthritis therapeutics include celecoxib, diclofenac sodium, rofecoxib, nabumetone, diclofenac sodium and misoprostol, oxaprozin, meloxicam, piroxicam, etodolac, naproxen, hylan G-F 20, leflunomide, tenoxicam, and naproxen sodium.
  • celecoxib may be incorporated into the encapsulated products of the present invention to effectively deliver celecoxib to a patient in need thereof.
  • celecoxib can be formulated with the present invention in doses ranging from about 150 to 250 mg daily, with 200 mg daily being the preferred dosage.
  • doses ranging from about 150 to 250 mg daily, with 200 mg daily being the preferred dosage.
  • One of ordinary skill in the art will be able to determine the proper dosage for the remaining disclosed drugs.
  • all the examples are non-limiting and it will be understood that other osteoarthritis and rheumatoid arthritis therapeutics from the disclosed classes may also be used with the present inventive subject matter.
  • Another preferred active material used in the composition of the present invention is a therapeutic useful for treating benign prostatic hypertrophy.
  • Benign prostatic hypertrophy is defined as an adenomatous hyperplasia of the periurethral part of the prostrate gland.
  • Classes of drug useful for the treatment of benign prostatic hypertrophy include alpha blockers, alpha-1 selective adrenoceptor blocking agents and 5-reductase inhibitors.
  • Specific examples of benign prostatic hypertrophy therapeutics include doxazosin mesylate, terazosin HCl, tamsulosin, finasteride, tamsulosin HCl, ethinyl estradiol and levonorgestrel .
  • doxazosin mesylate may be incorporated into encapsulated products of the present invention to effectively deliver doxazosin mesylate to a patient in need thereof.
  • doxazosin mesylate can be formulated with the present invention in doses ranging from about 1 to 16 mg daily.
  • doses ranging from about 1 to 16 mg daily.
  • One of ordinary skill in the art will be able to determine the proper dosage for the remaining disclosed drugs.
  • all the examples are non-limiting and it will be understood that other benign prostatic hypertrophy therapeutics from the disclosed classes may also be used with the present inventive subject matter.
  • Yet another preferred active material used in the composition of the present invention is a drug indicated for the treatment of fungal infections.
  • Classes of drugs indicated for the treatment of fungal infections include synthetic triazole, ergosterol inhibitor, and polyene antifungal. Specific examples of drugs indicated for the treatment of fungal infections are itraconazole, ketoconazole, and amphotericin B.
  • itraconazole may be incorporated into the encapsulated products of the present invention to effectively deliver itraconazole to a patient in need thereof.
  • itraconazole can be formulated with the present invention in doses ranging from about 1.0 to 400 mg daily.
  • doses ranging from about 1.0 to 400 mg daily.
  • One of ordinary skill in the art will be able to determine the proper dosage for the remaining disclosed drugs.
  • all the examples are non-limiting and it will be understood that other anti-fungals from the disclosed classes may also be used with the present inventive subject matter.
  • Still yet another preferred active material used in the composition of the present invention is a anti-convulsant .
  • Anti-convulsants are drugs that prevent or relieve convulsions wherein the convulsions are due to epilepsy, seizure disorders, partial seizure disorders or Huntington's disease.
  • Classes of drugs useful for treating these conditions include gamma-aminobutyric analogs, phenyltriazine, antiepileptic agents, benzodiazepines, polysynaptic response inhibitors, sulfamate-substituted monosaccharides, gamma-amino butyric acid uptake inhibitors and benzamides. Specific examples include carbamazepine, topiramate, and tigabine HCl.
  • carbamazepine may be incorporated into the encapsulated products of the present invention to effectively deliver carbamazepine to a patient in need thereof.
  • carbamazepine can be formulated with the present invention in doses ranging from about 100 to 1600 mg daily.
  • doses ranging from about 100 to 1600 mg daily.
  • One of ordinary skill in the art will be able to determine the proper dosage for the remaining disclosed drugs.
  • all the examples are non-limiting and it will be understood that other anti-convulsants from the disclosed classes may also be used with the present inventive subject matter.
  • Another preferred active material used in the composition of the present invention is an anti-herpetic.
  • Anti-herpetics are used to treat infections from the varicella-zoster virus.
  • Classes of drugs useful for treating herpes include synthetic purine nucleoside analogs, nucleoside analogs, and antiviral agents. Specific examples include acyclovir, valacyclovir HCL and famcyclovir.
  • acyclovir may be incorporated into the encapsulated products of the present invention to effectively deliver acyclovir to a patient in need thereof.
  • acyclovir can be formulated with the present invention in doses ranging from about 200 to 800 mg daily.
  • One of ordinary skill in the art will be able to determine the proper dosage for the remaining disclosed drugs.
  • anti-diarrheal therapeutics treat the condition of diarrhea whether it is symptomatic of the disorder itself wherein diarrhea is a condition that occurs when a mammal has a low amount of stool in a bowel movement. Diarrhea results mainly from excess fecal water in the bowel of the mammal.
  • Specific examples of anti-diarrheal therapeutics include loperamide HCl, diphenoxylate, codeine phosphate, camphorated opium tincture.
  • he encapsulated product includes the incorporation of flavors.
  • the flavoring agents which may be used include those flavors known to the skilled artisan, such as natural and artificial flavors. These flavorings may be chosen from synthetic flavor oils and flavoring aromatics and/or oils, oleoresins and extracts derived from plants, leaves, flowers, fruits, and so forth, and combinations thereof.
  • Nonlimiting representative flavor oils include spearmint oil, cinnamon oil, oil of wintergreen (methyl salicylate) , peppermint oil, clove oil, bay oil, anise oil, eucalyptus oil, thyme oil, cedar leaf oil, oil of nutmeg, allspice, oil of sage, mace, oil of bitter almonds, and cassia oil.
  • Also useful flavorings are artificial, natural and synthetic fruit flavors such as vanilla, and citrus oils including, without limitation, lemon, orange, lime, grapefruit, and fruit essences including apple, pear, peach, grape, strawberry, raspberry, cherry, plum, pineapple, apricot and so forth. These flavoring agents may be used in liquid or solid form and may be used individually or in admixture.
  • Commonly used flavors include mints such as peppermint, menthol, artificial vanilla, cinnamon derivatives, and various fruit flavors, whether employed individually or in admixture.
  • Other useful flavorings include aldehydes and esters such as cinnamyl acetate, cinnamaldehyde, citral diethylacetal, dihydrocarvyl acetate, eugenyl formate, p-methylamisol, and so forth may be used.
  • the liquid flavor is first absorbed onto a solid absorbent.
  • absorbents on which the liquid may be absorbed include, without limitation, silica gel particles, starches, carbohydrates such as sugars and polyhydroxyalcohols, celluloses, calcium salts such as calcium phosphate, calcium carbonate, and calcium sulfonate, and other absorbing agents in free-flowing powder form.
  • the amount of liquid flavor added depends on the final concentration desired. Generally, though, the liquid flavor will be present in quantities from about 0.1% to 70% by weight of the resultant flavor/absorbent mixture.
  • the flavor/absorbent mixture is then mixed with a the erodible polymer above.
  • the final mixture is then formed into the encapsulated product of the present invention by using a tableting machine.
  • the stations of the tableting machine are set to the desired caplet size, which is from about 1 millimeter to about 7 millimeters diameter and length for the encapsulated.
  • flavor with the active ingredient in the encapsulated product allows for flexibility in adding flavor to food items, confectionery products or chewing gum products. For example, delivery of two or more flavors to a single food item is possible by using encapsulated products containing different flavors in the food item. The delivery of two or more flavors is also possible in confectionery products and chewing gum products.
  • Advantages of preparing the inventive encapsulated product in this manner are that no heat and no moisture are needed in this process. Additionally and surprisingly, high concentrations of active ingredients may be incorporated into the final encapsulated product .
  • the encapsulated product of the present inventive subject matter is small enough that when the confectionery or chewing gum product is chewed, the encapsulated product can pass with the saliva and not be disformed by the teeth of the individual chewing.
  • vitamins that are available as active ingredients include, without limitation, vitamin A (retinol) , vitamin D (cholecalciferol) , vitamin E group ( ⁇ -tocopherol and other tocopherols) , vitamin K group ( phylloquinones and menaquinones) , thiamine (vitamin B x ) , riboflavin (vitamin B 2 ) , niacin, vitamin B 6 group, folic acid, vitamin B 12 (cobalamins) , biotin, vitamin C (ascorbic acid), and mixtures thereof.
  • vitamin A retinol
  • vitamin D cholesterolcalciferol
  • vitamin E group ⁇ -tocopherol and other tocopherols
  • vitamin K group phylloquinones and menaquinones
  • thiamine vitamin B x
  • riboflavin vitamin B 2
  • niacin vitamin B 6 group
  • vitamin B 12 cobalamins
  • biotin vitamin C (ascorbic acid), and mixtures thereof
  • the amount of vitamin or vitamins present in the final encapsulated product of the present inventive subject matter is dependent on the particular vitamin and is generally the United States' Department of Agriculture Recommended Daily Allowances (USRDA) for that vitamin.
  • USRDA United States' Department of Agriculture Recommended Daily Allowances
  • Vitamin C is the active ingredient and the encapsulated product is being used in a confectionery or chewing gum targeting adults
  • the amount of vitamin C in the encapsulated product would be 60 milligrams, which is the USRDA of vitamin C for adults.
  • minerals that are available as active ingredients include, without limitation, calcium, magnesium, phosphorus, iron, zinc, iodine, selenium, potassium, copper, manganese, molybdenum and mixtures thereof.
  • vitamins the amount of mineral or minerals present in the final encapsulated product of the present inventive subject matter is dependent on the particular mineral and is generally the USRDA for that mineral. For example, if iodine is the active ingredient and the encapsulated product is being used in a confectionery or chewing gum targeting adults, the amount of iodine in the encapsulated product would be 150 micrograms, which is the USRDA of iodine for adults.
  • herbals that are available as active ingredients include, without limitation, echinacea, peppermint, licorice, goldenseal, panax pseudoginseng, grapeseed extract, bilberry, kava, ginko biloba, panax quinquefolium, Siberian ginseng, St. John's wort, bromelian, guglupids, hawthorn, garlic, ginger, angelica species, dandelion, goldenseal, and mixtures thereof.
  • examples of spices that are available as active ingredients include, without limitation, mustard, dillweed, cinnamon, garlic, black pepper, onion, sage, oregano, basil, cream of tartar, targon, cayenne pepper, red pepper, and mixtures thereof. This list of herbals and spices is for exemplary purposes and is not meant to be construed as limiting the inventive subject matter thereto.
  • an advantage of method of the inventive subject matter is that no heat nor moisture is required for forming the encapsulated product.
  • the encapsulated product of the present inventive subject matter has a uniform active ingredient content and may be strong enough to withstand mechanical pressure both in the processing of the product, and in the chewing of the product in the mouth so that the active ingredients are released in the stomach.
  • dimenhydrinate was mixed with 51.31% hydroxypropyl methyl cellulose in a shear mixer. The mixture was then granulated using 3.91% povidone K30 dissolved in isopropyl alcohol. The granulated mixture was passed through a no. 10 mesh and allowed to air dry. When the granulated mixture was dry, it was then passed through a no. 20 mesh. The mixture was next lubricated with 1.30% magnesium stearate. The final mixture was mixed for 3 minutes. The mixture was loaded into a tableting machine. A series of caplets was produced using 20 KN of force. Each caplet weighed 19 mg and six caplets were filled in a no. 2 capsule to obtain a 50-mg dimenhydrinate capsule.
  • the 50-mg capsule was then tested in vi tro for dissolution characteristics.
  • the capsule was loaded into a no. 2 apparatus (paddle, USP) with 900 ml of water.
  • the capsule was rotated at 50 rpm (revolutions per minute) and the amount dissolved was determined at 30, 60, 120, 180, 240, 360 and 480 minutes.
  • nifedipine was mixed with 10.90% lactose anhydrous, 0.90% icrocrystalline cellulose, and 48.90% hydroxypropyl methyl cellulose in a shear mixer. The mixture was then granulated using 4.20% povidone K30 dissolved in isopropyl alcohol. The granulated mixture was passed through a no . 10 mesh and allowed to air dry. When the granulated mixture was dry, it was then passed through a no. 20 mesh. The mixture was next lubricated with 1.00% magnesium stearate. The final mixture was mixed for 3 minutes. The mixture was loaded into a tableting machine.
  • caplets were produced using 20 KN of force. Each caplet weighed 17.60 mg and five caplets were filled in a no. 2 capsule to obtain a 30-mg nifedipine capsule. The 30-mg capsule was then tested in vi tro for dissolution characteristics. The capsule was loaded into a no. 2 apparatus (paddle, USP) with 900 ml of water (phosphate buffer pH: 6.8). The capsule was rotated at 50 rpm (revolutions per minute) and the amount dissolved was determined at 1, 2, 5, 7 and 9 hours
  • nifedipine was mixed with 20.00% lactose anhydrous, 1.00% microcrystalline cellulose, and 38.90% hydroxypropyl methyl cellulose (19.45% HPMC K15 M and 19.45% HPMC K100 M) in a shear mixer. The mixture was then granulated using 5.00% povidone K30 dissolved in isopropyl alcohol. The granulated mixture was passed through a no. 10 mesh and allowed to air dry. When the granulated mixture was dry, it was then passed through a no. 20 mesh. The mixture was next lubricated with 1.00% magnesium stearate. The final mixture was mixed for 3 minutes. The mixture was loaded into a tableting machine.
  • caplets A series of caplets was produced using 20 KN of force. Each caplet weighed 17.57 mg and five caplets were filled in a no. 2 capsule to obtain a 30-mg nifedipine capsule.
  • the 30-mg capsule was then tested in vi tro for dissolution characteristics.
  • the capsule was loaded into a no. 2 apparatus (paddle, USP) with 900 ml of water (phosphate buffer pH: 6.8).
  • the capsule was rotated at 50 rpm (revolutions per minute) and the amount dissolved was determined at 1, 2, 5, 7 and 9 hours
  • nifedipine was mixed with 20.00% lactose anhydrous, 1.00% microcrystalline cellulose, and 38.90% hydroxypropyl methyl cellulose (11.67% HPMC K15 M and 27.23% HPMC K100 M) in a shear mixer. The mixture was then granulated using 5.00% povidone K30 dissolved in isopropyl alcohol. The granulated mixture was passed through a no. 10 mesh and allowed to air dry. When the granulated mixture was dry, it was then passed through a no. 20 mesh. The mixture was next lubricated with 1.00% magnesium stearate. The final mixture was mixed for 3 minutes. The mixture was loaded into a tableting machine.
  • caplets A series of caplets was produced using 20 KN of force. Each caplet weighed 17.57 mg and five caplets were filled in a no. 2 capsule to obtain a 30-mg nifedipine capsule.
  • the 30-mg capsule was then tested in vi tro for dissolution characteristics.
  • the capsule was loaded into a no. 2 apparatus (paddle, USP) with 900 ml of water (phosphate buffer pH: 6.8).
  • the capsule was rotated at 50 rpm (revolutions per minute) and the amount dissolved was determined at 1, 2, 5, 7 and 9 hours
  • caplets were produced using 20 KN of force. Each caplet weighed 23.00 mg. Six of the caplets were coated using a film coating comprising 70% cellulose acetate phtalate as a film forming agent and 30% triethylcitrate as a plasticizer. At the same time, 9 caplets were coated using a film coating comprising 70% eudragit RS as a film forming agent and 30% dibutylphtalate as a plasticizer. The fifteen coated caplets were filled in a size 0 capsule to obtain a 250-mg mesalamine capsule.
  • 87.0% clindamycin hydrochloride was mixed with 7.8% microcrystalline cellulose in a shear mixer. The mixture was then granulated using 3.9% povidone K30 dissolved in isopropyl alcohol. The granulated mixture was passed through a no. 10 mesh and allowed to air dry. When the granulated mixture was dry, it was then passed through a no. 20 mesh. The mixture was next lubricated with 1.3% magnesium stearate. The final mixture was mixed for 3 minutes. The mixture was loaded into a tableting machine.
  • caplets were produced using 20 KN of force. Each caplet weighed 23.00 mg. Seven of the caplets were coated using a film coating comprising 70% cellulose acetate phtalate as a film forming agent and 30% triethylcitrate as a plasticizer. At the same time, eight caplets were coated using a film coating comprising 70% HPC as a film forming agent and 30% dibutylphtalate as a plasticizer. The fifteen coated caplets were filled in a size 0 capsule to obtain a 300-mg clindamycin hydrochloride capsule.

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Abstract

La présente invention concerne un nouveau produit encapsulé à libération prolongée ou contrôlée qui comprend: au moins un ingrédient actif, au moins un polymère érodable et au moins une matière lubrifiante, ledit produit encapsulé se présentant sous forme d'un caplet d'un diamètre compris entre environ 1 millimètre et environ 7 millimètres et d'une longueur comprise entre environ 1 millimètre et environ 7 millimètres. Cette invention concerne également un procédé de préparation dudit produit encapsulé.
PCT/US2001/047180 2001-07-31 2001-12-06 Produits d'encapsulation assurant une liberation controlee ou prolongee WO2003011205A2 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
AU2002239555A AU2002239555A1 (en) 2001-07-31 2001-12-06 Encapsulation products for controlled or extended release
EP01987325A EP1581160A4 (fr) 2001-07-31 2001-12-06 Produits d'encapsulation assurant une liberation controlee ou prolongee

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US30856801P 2001-07-31 2001-07-31
US60/308,568 2001-07-31
US09/982,092 US20020044962A1 (en) 2000-06-06 2001-10-19 Encapsulation products for controlled or extended release
US09/982,092 2001-10-19

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WO2003011205A2 true WO2003011205A2 (fr) 2003-02-13
WO2003011205A3 WO2003011205A3 (fr) 2003-06-19

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2468264A1 (fr) * 2010-12-27 2012-06-27 Laboratorios Liconsa, S.A. Comprimé pharmaceutique oral pour la libération prolongée de mésalazine et son procédé de fabrication
US9393192B2 (en) 2002-07-29 2016-07-19 Alza Corporation Methods and dosage forms for controlled delivery of paliperidone and risperidone

Families Citing this family (73)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
SE0000774D0 (sv) * 2000-03-08 2000-03-08 Astrazeneca Ab New formulation
SE0000773D0 (sv) * 2000-03-08 2000-03-08 Astrazeneca Ab New formulation
US7674480B2 (en) * 2000-06-23 2010-03-09 Teva Pharmaceutical Industries Ltd. Rapidly expanding composition for gastric retention and controlled release of therapeutic agents, and dosage forms including the composition
GB0018968D0 (en) * 2000-08-02 2000-09-20 Pfizer Ltd Particulate composition
US8206741B2 (en) 2001-06-01 2012-06-26 Pozen Inc. Pharmaceutical compositions for the coordinated delivery of NSAIDs
EA006398B1 (ru) 2001-06-01 2005-12-29 Поузен Инк. Фармацевтические композиции для координированной доставки нестероидных противовоспалительных лекарственных средств
US6663896B1 (en) * 2001-08-01 2003-12-16 Alvin S. Blum Delayed release aspirin for vascular obstruction prophylaxis
SE0102993D0 (sv) 2001-09-07 2001-09-07 Astrazeneca Ab New self emulsifying drug delivery system
US20050215552A1 (en) * 2002-05-17 2005-09-29 Gadde Kishore M Method for treating obesity
AR039744A1 (es) * 2002-06-26 2005-03-09 Alza Corp Metodos y formas de dosificacion para aumentar la solubilidad de las composiciones de farmacos para la administracion controlada
US20050208132A1 (en) * 2002-07-29 2005-09-22 Gayatri Sathyan Methods and dosage forms for reducing side effects of benzisozazole derivatives
WO2004010970A1 (fr) * 2002-07-29 2004-02-05 Alza Corporation Formulations et formes posologiques pour une administration controlee de topiramate
WO2004026256A2 (fr) * 2002-09-20 2004-04-01 Alpharma, Inc. Preparations d'opioides a liberation soutenue et methodes d'utilisation
US20070077301A1 (en) * 2002-12-23 2007-04-05 Meyer Glenn A Venlafaxine osmotic device formulation
CA2415154C (fr) * 2002-12-24 2009-06-16 Biovail Laboratories Inc. Preparations a liberation modifiee contenant des inhibiteurs selectifs de la recapture de la serotonine
US20080213363A1 (en) * 2003-01-23 2008-09-04 Singh Nikhilesh N Methods and compositions for delivering 5-HT3 antagonists across the oral mucosa
US20040186155A1 (en) * 2003-01-30 2004-09-23 Dayno Jeffrey Marc Combination therapy for the treatment or prevention of migraine
US20040156953A1 (en) * 2003-02-12 2004-08-12 Guidry Ray A. Encapsulated food additives and method for preparing foodstuffs
US20050220870A1 (en) * 2003-02-20 2005-10-06 Bonnie Hepburn Novel formulation, omeprazole antacid complex-immediate release for rapid and sustained suppression of gastric acid
EP1603537A4 (fr) * 2003-02-20 2009-11-04 Santarus Inc Liberation immediate d'un complexe antacide d'omeprazole presentant une nouvelle formulation pour une elimination rapide et prolongee d'acide gastrique
EP1601652B1 (fr) * 2003-03-03 2008-07-30 Mycosol, Inc. Sels de pyridinium, composes et procedes d'utilisation
ES2303085T3 (es) 2003-04-29 2008-08-01 Orexigen Therapeutics, Inc. Composiciones que afectan a la perdida de peso.
US20050037070A1 (en) * 2003-07-18 2005-02-17 Santarus, Inc. Pharmaceutical formulatins useful for inhibiting acid secretion and methods for making and using them
TWI337877B (en) * 2003-07-18 2011-03-01 Santarus Inc Pharmaceutical formulation and method for treating acid-caused gastrointestinal disorders
US8993599B2 (en) * 2003-07-18 2015-03-31 Santarus, Inc. Pharmaceutical formulations useful for inhibiting acid secretion and methods for making and using them
GB0317904D0 (en) * 2003-07-31 2003-09-03 Jagotec Ag Improvements in or relating to organic compounds
CA2534920A1 (fr) * 2003-08-06 2005-02-24 Alza Corporation Administration reguliere de topiramate pendant une periode prolongee a formulation de dispersion amelioree
US20050042281A1 (en) * 2003-08-21 2005-02-24 Singh Nikhilesh N. Compositions for delivering therapeutic agents across the oral mucosa
EP1658048A2 (fr) * 2003-08-22 2006-05-24 ALZA Corporation Administration progressive de topiramate sur une duree prolongee
US20050175696A1 (en) * 2003-12-29 2005-08-11 David Edgren Drug granule coatings that impart smear resistance during mechanical compression
MXPA06007510A (es) * 2003-12-29 2009-06-10 Johnson & Johnson Composiciones de farmaco y formas de dosis novedosas de topiramato.
CA2551815A1 (fr) * 2003-12-29 2005-07-21 Alza Corporation Compositions medicamenteuses et formes pharmaceutiques
EP1718303A4 (fr) * 2004-02-10 2010-09-01 Santarus Inc Combinaison d'un inhibiteur de la pompe a protons, d'un tampon et d'un medicament anti-inflammatoire non steroidien
KR100598326B1 (ko) 2004-04-10 2006-07-10 한미약품 주식회사 ＨＭＧ-ＣｏＡ 환원효소 억제제의 경구투여용 서방형 제제및 이의 제조방법
US20050239845A1 (en) * 2004-04-16 2005-10-27 Santarus, Inc. Combination of proton pump inhibitor, buffering agent, and prokinetic agent
US8545881B2 (en) 2004-04-19 2013-10-01 Eurand Pharmaceuticals, Ltd. Orally disintegrating tablets and methods of manufacture
US8815916B2 (en) * 2004-05-25 2014-08-26 Santarus, Inc. Pharmaceutical formulations useful for inhibiting acid secretion and methods for making and using them
US8906940B2 (en) * 2004-05-25 2014-12-09 Santarus, Inc. Pharmaceutical formulations useful for inhibiting acid secretion and methods for making and using them
JP4880591B2 (ja) 2004-06-04 2012-02-22 テバ ファーマシューティカル インダストリーズ リミティド イルベサルタンを含む医薬組成物
AU2005264864B2 (en) 2004-06-16 2011-08-11 Takeda Pharmaceutical Company Limited Multiple PPI dosage form
EP1863449A2 (fr) * 2005-03-28 2007-12-12 Dexcel Pharma Technologies Ltd. Absorption regulee de statines dans l'intestin
EP2292220A3 (fr) 2005-11-22 2012-01-04 Orexigen Therapeutics, Inc. Compositions et procédés pour augmenter la sensibilité à l'insuline
JP2009517394A (ja) * 2005-11-28 2009-04-30 オレキシジェン・セラピューティクス・インコーポレーテッド ゾニサミドの徐放性製剤
US20080069889A1 (en) * 2006-03-07 2008-03-20 Cherukuri S R Compressible resilient granules and formulations prepared therefrom
US20070243248A1 (en) * 2006-04-14 2007-10-18 Cherukuri S Rao Rapidly disintegrating solid oral dosage form of liquid dispersions
CN101431895A (zh) * 2006-05-01 2009-05-13 卡普里康制药公司 新颖的曲坦制剂和制备它们的方法
US8916195B2 (en) * 2006-06-05 2014-12-23 Orexigen Therapeutics, Inc. Sustained release formulation of naltrexone
WO2008005318A2 (fr) * 2006-06-29 2008-01-10 Capricorn Pharma Inc. Produits à mâcher et procédés d'élaboration
CL2007002214A1 (es) * 2006-08-14 2008-03-07 Boehringer Ingelheim Int Composicion farmaceutica en la forma de comprimido, donde al menos la longitud del comprimido en el estado anterior de la aplicacion es al menos 7/12 del diametro pilorico del paciente y despues de ingerirlo en estado alimentado, la longitud del comp
WO2008027557A2 (fr) * 2006-08-31 2008-03-06 Spherics, Inc. Compositions à base de topiramate et méthodes permettant d'en augmenter la biodisponibilité
US20080081072A1 (en) * 2006-09-30 2008-04-03 Cherukuri S R Resin-complex granulation for water-soluble drugs and associated methods
US20080081067A1 (en) * 2006-10-03 2008-04-03 Gupta Manishkumar Sustained release pharmaceutical compositions of venlafaxine and process for preparation thereof
US20090092658A1 (en) * 2007-10-05 2009-04-09 Santarus, Inc. Novel formulations of proton pump inhibitors and methods of using these formulations
KR20180066272A (ko) 2006-11-09 2018-06-18 오렉시젠 세러퓨틱스 인크. 단위 용량 팩키지
EP2089005B1 (fr) 2006-11-09 2010-03-17 Orexigen Therapeutics, Inc. Formulations pharmaceutiques en couches comprenant une couche intermédiaire à dissolution rapide
DE07870164T1 (de) * 2006-11-17 2009-02-19 Supernus Pharmaceuticals, Inc. Verzögert freigesetzte formulierungen aus topiramat
MX2009005446A (es) * 2006-11-22 2009-06-02 Organon Nv Sistema de suministro vaginal para mirtazapina.
WO2008076287A2 (fr) * 2006-12-13 2008-06-26 Tuel Stephen M Procédés destinés à fabriquer des composants pharmaceutiques pour des produits médicamenteux personnalisés
US20090285889A1 (en) * 2008-05-14 2009-11-19 Capricom Pharma Inc. Modified release formulations of dihydropyridine compounds and methods of making same
JP2011521973A (ja) 2008-05-30 2011-07-28 オレキシジェン・セラピューティクス・インコーポレーテッド 内臓脂肪の状態を処置するための方法
CA2736547C (fr) 2008-09-09 2016-11-01 Pozen Inc. Procede d'administration d'une composition pharmaceutique a un patient en ayant besoin
EP2445344A4 (fr) * 2009-06-25 2013-01-23 Pozen Inc Procédé de traitement d'un patient nécessitant une thérapie à l'aspirine
MX2011013467A (es) 2009-06-25 2012-02-13 Astrazeneca Ab Metodo para tratar un paciente que corre el riesgo de desarollar una ulcera asociada a antiinflamatorio no esteroide (aine).
CA2785822C (fr) 2010-01-11 2019-06-25 Orexigen Therapeutics, Inc. Methodes permettant de faire perdre du poids a des patients souffrant d'une depression severe
US9511037B2 (en) * 2010-04-23 2016-12-06 Genco Sciences Llc Compositions for reduction of side effects
EP2560624B1 (fr) * 2010-04-23 2018-07-04 KemPharm, Inc. Formulation thérapeutique visant à réduire les effets secondaires de médicaments
BR112014016085A8 (pt) 2011-12-28 2017-07-04 Pozen Inc composições aprimoradas e métodos para distribuição de omeprazol mais ácido acetilsalicílico
US9633575B2 (en) 2012-06-06 2017-04-25 Orexigen Therapeutics, Inc. Methods of treating overweight and obesity
US20140141075A1 (en) * 2012-11-21 2014-05-22 Warner Chilcott Company, Llc 5-aminosalicylic acid capsule formulation
WO2014184662A2 (fr) * 2013-03-14 2014-11-20 Redhill Biopharma Ltd. Formes posologiques solides à libération prolongée d'antiémétiques
CN106456611B (zh) 2014-03-11 2021-07-20 红山生物医药有限公司 用于治疗恶心、呕吐或腹泻症状的恩丹西酮缓释固体制剂
GB2571696B (en) 2017-10-09 2020-05-27 Compass Pathways Ltd Large scale method for the preparation of Psilocybin and formulations of Psilocybin so produced
AU2020259406A1 (en) 2019-04-17 2021-11-04 Compass Pathfinder Limited Treatment of depression and other various disorders with psilocybin

Family Cites Families (23)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4568560A (en) * 1984-03-16 1986-02-04 Warner-Lambert Company Encapsulated fragrances and flavors and process therefor
GB2176999B (en) * 1985-06-22 1989-07-12 Stanley Stewart Davis Sustained release medicament
US4740376A (en) * 1986-01-07 1988-04-26 Warner-Lambert Company Encapsulation composition for use with chewing gum and edible products
DE3610037A1 (de) * 1986-03-21 1987-09-24 Schering Ag Nifedipinkombinationspraeparat
US5004595A (en) * 1986-12-23 1991-04-02 Warner-Lambert Company Multiple encapsulated flavor delivery system and method of preparation
US4981698A (en) * 1986-12-23 1991-01-01 Warner-Lambert Co. Multiple encapsulated sweetener delivery system and method of preparation
US4975270A (en) * 1987-04-21 1990-12-04 Nabisco Brands, Inc. Elastomer encased active ingredients
US5073380A (en) * 1987-07-27 1991-12-17 Mcneil-Ppc, Inc. Oral sustained release pharmaceutical formulation and process
US5266335A (en) * 1990-05-04 1993-11-30 Warner-Lambert Company Microencapsulated flavoring agents and methods for preparing same
US5460824A (en) * 1990-06-27 1995-10-24 Warner-Lambert Company Method for the preparation of an encapsulated medicament
IT1250483B (it) * 1990-08-30 1995-04-07 Eurand Int Sistema di ritardo a matrice multipla
US5215758A (en) * 1991-09-11 1993-06-01 Euroceltique, S.A. Controlled release matrix suppository for pharmaceuticals
US5869097A (en) * 1992-11-02 1999-02-09 Alza Corporation Method of therapy comprising an osmotic caplet
US5451409A (en) * 1993-11-22 1995-09-19 Rencher; William F. Sustained release matrix system using hydroxyethyl cellulose and hydroxypropyl cellulose polymer blends
US5637313A (en) * 1994-12-16 1997-06-10 Watson Laboratories, Inc. Chewable dosage forms
US5773031A (en) * 1996-02-27 1998-06-30 L. Perrigo Company Acetaminophen sustained-release formulation
EP0951278A2 (fr) * 1997-01-03 1999-10-27 ELAN CORPORATION, Plc Formulation de minicomprimes de cisapride a liberation prolongee
US5972916A (en) * 1997-07-14 1999-10-26 Bristol-Myers Squibb Company Compositions containing the nonprescription combination of acetaminophen, aspirin and caffeine to alleviate the pain and symptoms of migraine
DE19842753A1 (de) * 1998-09-18 2000-03-23 Bayer Ag Agitationsunabhängige pharmazeutische Retardzubereitungen und Verfahren zu ihrer Herstellung
DE19848260C2 (de) * 1998-10-20 2002-01-17 Fumapharm Ag Muri Fumarsäure-Mikrotabletten
DE19901683B4 (de) * 1999-01-18 2005-07-21 Grünenthal GmbH Analgetikum mit kontrollierter Wirkstofffreisetzung
US6352721B1 (en) * 2000-01-14 2002-03-05 Osmotica Corp. Combined diffusion/osmotic pumping drug delivery system
IT1318625B1 (it) * 2000-07-14 2003-08-27 Roberto Valducci Formulazioni farmaceutiche solide orali a rilascio multifasicoph-dipendente.

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9393192B2 (en) 2002-07-29 2016-07-19 Alza Corporation Methods and dosage forms for controlled delivery of paliperidone and risperidone
EP2468264A1 (fr) * 2010-12-27 2012-06-27 Laboratorios Liconsa, S.A. Comprimé pharmaceutique oral pour la libération prolongée de mésalazine et son procédé de fabrication
WO2012089677A1 (fr) * 2010-12-27 2012-07-05 Laboratorios Liconsa, S. A. Comprimé pharmaceutique oral pour la libération contrôlée de la mésalazine et son procédé d'obtention
CN103269691A (zh) * 2010-12-27 2013-08-28 利肯萨实验室股份有限公司 用于控制释放美沙拉嗪的口服药物片剂和其获得方法
JP2014501267A (ja) * 2010-12-27 2014-01-20 ラボラトリオス リコンサ、ソシエダード、アノニマ メサラジン制御放出用の経口用医薬錠剤および前記錠剤を得るための製法

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EP1581160A4 (fr) 2009-08-12

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